Cyclooxygenase is known to be important in physiologic functions such as inflammation and pain modulation. Recently, an inducible form of this enzyme, Cyclooxygenase)2 (COX-2),was discovered. COX-2 induced by inflammatory mediators such as IL)lB, as well as agents known to activate protein kinase-C (i.e. phorbol esters like TPA), possibly through NF)kB. To better understand the mechanisms of prostaglandlin production in the CNS, we have examined COX-2 activity and expression in primary astrocytes cultures. We demonstrate synergistic increase in prostaglandlin accumulation and COX-2 activity with the application of lL)1B and TPA, and postulate that these agents are working through a common pathway mediated by NF)kB.